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1.
Biochemistry (Mosc) ; 83(2): 140-151, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29618300

RESUMO

Binding to Na+,K+-ATPase, cardiotonic steroids (CTS) activate intracellular signaling cascades that affect gene expression and regulation of proliferation and apoptosis in cells. Ouabain is the main CTS used for studying these processes. The effects of other CTS on nervous tissue are practically uncharacterized. Previously, we have shown that ouabain affects the activation of mitogen-activated protein kinases (MAP kinases) ERK1/2, p38, and JNK. In this study, we compared the effects of digoxin and bufalin, which belong to different subclasses of CTS, on primary culture of rat cortical cells. We found that CTS toxicity is not directly related to the degree of Na+,K+-ATPase inhibition, and that bufalin and digoxin, like ouabain, are capable of activating ERK1/2 and p38, but with different concentration and time profiles. Unlike bufalin and ouabain, digoxin did not decrease JNK activation after long-term incubation. We concluded that the toxic effect of CTS in concentrations that inhibit less than 80% of Na+,K+-ATPase activity is related to ERK1/2 activation as well as the complex profile of MAP kinase activation. A direct correlation between Na+,K+-ATPase inhibition and the degree of MAP kinase activation is only observed for ERK1/2. The different action of the three CTS on JNK and p38 activation may indicate that it is associated with intracellular signaling cascades triggered by protein-protein interactions between Na+,K+-ATPase and various partner proteins. Activation of MAP kinase pathways by these CTS occurs at concentrations that inhibit Na+,K+-ATPase containing the α1 subunit, suggesting that these signaling cascades are realized via α1. The results show that the signaling processes in neurons caused by CTS can differ not only because of different inhibitory constants for Na+,K+-ATPase.


Assuntos
Bufanolídeos/metabolismo , Digoxina/metabolismo , Neurônios/metabolismo , Ouabaína/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Bufanolídeos/química , Bufanolídeos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cérebro/citologia , Digoxina/química , Digoxina/toxicidade , Ativação Enzimática/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Microssomos/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ouabaína/química , Ouabaína/toxicidade , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
2.
Mikrobiol Z ; 56(6): 51-7, 1994.
Artigo em Russo | MEDLINE | ID: mdl-7894729

RESUMO

State of microbiocenosis of large intestine in rats and furo subjected to constant combined irradiation has been studied in full-scale experiments in the emergency rooms of the Chernobyl NPP and in the nearest zone of its effect. The higher diversity of microflora (as compared to initial one), sharp increase of the amount of Candida genus fungi, a decrease of the number of bifidobacteria and increase of the amount of conditionally pathogenic flora were observed in rats with the dose of external irradiation of 1.43 Gr absorbed for 14 days. The expressed associative character of disbioses is distinctly traced. In furo affected by the radion exceeding the background level feeding with products contaminated by radionuclides leads to changes whose individual character corresponds to the picture of disbiosis under radiation injury.


Assuntos
Exposição Ambiental/efeitos adversos , Intestino Grosso/microbiologia , Intestino Grosso/efeitos da radiação , Centrais Elétricas , Liberação Nociva de Radioativos , Poluentes Radioativos/efeitos adversos , Animais , Fezes/microbiologia , Masculino , Ratos , Ucrânia
3.
Tsitol Genet ; 26(2): 21-4, 1992.
Artigo em Russo | MEDLINE | ID: mdl-1615555

RESUMO

The bone marrow eosinophils of rats subjected to irradiation are capable of secreting a peroxidase system obtained by neutrophils and endotheliocytes. As a result, there appear heterophil granulocytes in the peripheral blood.


Assuntos
Medula Óssea/efeitos da radiação , Neutrófilos/efeitos da radiação , Animais , Medula Óssea/ultraestrutura , Raios gama , Contagem de Leucócitos , Neutrófilos/metabolismo , Neutrófilos/ultraestrutura , Peroxidases/metabolismo , Ratos , Ratos Endogâmicos
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